What are the 5 steps that take place in transmitting information across a synapse?

Synthesis and Storage of Neurotransmitters

This is the first step of synaptic transmission. Some neurotransmitters (eg acetylcholine, ACh) are synthesised in the axon, while others (eg neuropeptides) are made in the cell body.

• Acetylcholine– is synthesised within the synaptic terminal of the axon. Its precursors (choline, acetate) are taken into the cell by membrane channels or created as byproducts of other processes. Enzymes (such as choline acetyltransferase) convert precursors into the neurotransmitter.
• Endogenous opioids such as enkephalins– are an example of neuropeptides. These large neurotransmitters are produced within the cell body via transcription in the nucleus and translation in the endoplasmic reticulum. Synthesised precursors are then packaged into secretory granules and sent to the axonal terminal. Importantly, proteases present in the granules cleave the precursors into their mature neuropeptide form during this journey.

Once synthesised, neurotransmitters are stored in vesicles within the synaptic terminal until an action potential arrives, causing their release. Neurotransmitters such as acetylcholine are stored within the small synaptic vesicles, whereas neuropeptides reside within large dense-core vesicles.

Neurotransmitter Release

Action potentials depolarising the synaptic terminal lead to the opening of voltage-gated calcium channels. This allows an influx of calcium in the terminal and fusion of the synaptic vesicles with the cell membrane (exocytosis).  Consequently, the neurotransmitter is released into the synaptic cleft.

By OpenStax [CC BY 4.0 (https://creativecommons.org/licenses/by/4.0)], via Wikimedia Commons

Fig 2 – Diagram showing exocytosis, the process by which neurotransmitters are released into the synaptic cleft.

Postsynaptic Receptors

The neurotransmitter in the synaptic cleft diffuses across the gap to the post-synaptic membrane. Here, they can bind to two types of post-synaptic receptors.

This can cause either depolarisation to promote or hyperpolarisation to inhibit the action potential generation in the post-synaptic neurone.

Inactivation/Removal of Neurotransmitters

Once the post-synaptic membrane has responded the neurotransmitter in the synaptic cleft; it is either inactivated or removed. This can be done in several ways:

• Re-uptake – serotonin is taken back into the pre-synaptic neurone by the transporter proteins in the neuronal membrane. These neurotransmitters are subsequently either recycled by re-packaging into vesicles or broken down by enzymes.
• Breakdown – acetylcholine is broken down by acetylcholinesterase present in the synaptic cleft, inactivating the neurotransmitter.
• Diffusion into surrounding areas

Clinical Relevance – Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors are a class of drug that inhibits the activity of acetylcholinesterase within the synaptic cleft. This increases cholinergic transmission as more acetylcholine is present within the synaptic cleft for longer periods of time.

These drugs, such as pyridostigmine, rivastigmine, and donepezil, can be used to treat various conditions:

• Myasthenia gravis – the inhibition of acetylcholinesterase works at the neuromuscular junction rather than at the synaptic cleft to mitigate the effects of loss of nicotinic acetylcholine receptors.
• Alzheimer’s disease 
• Glaucoma
• To reverse the effect of non-depolarising muscle relaxants, such as rocuronium.

As cholinergic transmission is widespread throughout the body, particularly mediating the actions of parasympathetic nervous system, these drugs can cause many side effects such as bradycardia, hypotension, diarrhoea, excessive salivation or blurry vision.